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SNPs upstream of the minimal promoter control IL-2 expression and are candidates for the autoimmune disease-susceptibility locus Aod2/Idd3/Eae3

Genes & Immunity volume 9, pages 115–121 (2008)Cite this article

Abstract

IL-2, a T-cell growth and differentiation factor, plays an important role in immune homeostasis. Previously, we identified IL2 as a candidate for Aod2, a quantitative trait locus (QTL) controlling susceptibility to autoimmune ovarian dysgenesis (AOD) induced by day 3 neonatal thymectomy. Here, we report the identification of single-nucleotide polymorphisms (SNPs) in a region upstream of the minimal IL2 promoter (−2.8 kb to −300 bp), which distinguish AOD-susceptible A/J and AOD-resistant C57BL/6J (B6/J) mice. Six of the SNPs (−1010 C → T, −962 C → T, −926/−925 ΔΔ → AC, −921 T → C, −914 T → C and −674 G → A) contribute to the enhanced transcriptional activity of the extended B6/J promoter relative to A/J. Importantly, the −1010 SNP resides within a canonical AP-1-binding motif with the C → T transition at this site abrogating AP-1 binding. Moreover, these SNPs segregate with differential production of IL-2 by CD4+ T cells as well as susceptibility alleles at Idd3 and Eae3, QTL controlling insulin-dependent diabetes mellitus and experimental allergic encephalomyelitis. These are the first SNPs identified within the extended murine IL2 promoter that control differential IL-2 transcription in CD4+ T cells, and, as such, they are not only candidates for Aod2, but are also candidates for a shared autoimmune disease-susceptibility locus underlying Idd3 and Eae3.

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Acknowledgements

This work was supported by NIH Grants AI041747, AI058052, AI045666, NS036526 and AI051454.

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Authors and Affiliations

  1. Department of Medicine, University of Vermont, Burlington, VT, USA

    R del Rio, R Noubade, M Subramanian, N Saligrama, S Diehl, M Rincon & C Teuscher

  2. Department of Pathology, University of Vermont, Burlington, VT, USA

    N Saligrama & C Teuscher

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  1. R del Rio
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Correspondence to C Teuscher.

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del Rio, R., Noubade, R., Subramanian, M. et al. SNPs upstream of the minimal promoter control IL-2 expression and are candidates for the autoimmune disease-susceptibility locus Aod2/Idd3/Eae3. Genes Immun 9, 115–121 (2008). https://doi.org/10.1038/sj.gene.6364455

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